The multifactorial and complex nature of Alzheimer's disease (AD) has made it difficult to identify therapeutic targets that are causally involved in the disease process. However, accumulating evidence from experimental and clinical studies that investigate the early disease process point towards the required role of tau in AD etiology. Importantly, a large number of studies investigate and characterize the plethora of pathological forms of tau protein involved in disease onset and propagation. Immunotherapy is one of the most clinical approaches anticipated to make a difference in the field of AD therapeutics. Tau -targeted immunotherapy is the new direction after the failure of amyloid beta (Aß)-targeted immunotherapy and the growing number of studies that highlight the Aß-independent disease process. It is now well established that immunotherapy alone will most likely be insufficient as a monotherapy. Therefore, this review discusses updates on tau-targeted immunotherapy studies, AD-relevant tau species, updates on promising biomarkers and a prospect on combination therapies to surround the disease propagation in an efficient and timely manner.

中文翻译：

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AD tau 靶向免疫治疗的进展和考虑。

阿尔茨海默病 (AD) 的多因素和复杂性质使得很难确定与疾病过程有因果关系的治疗靶点。然而，从调查早期疾病过程的实验和临床研究中积累的证据表明 tau 在 AD 病因学中的必要作用。重要的是，大量研究调查和表征了参与疾病发作和传播的大量 tau 蛋白病理形式。免疫疗法是预计将在 AD 治疗领域产生影响的最具临床意义的方法之一。Tau 靶向免疫疗法是继淀粉样蛋白 β (Aß) 靶向免疫疗法失败以及越来越多的研究强调 Aß 非依赖性疾病过程之后的新方向。现在已经确定，单独的免疫疗法很可能不足以作为单一疗法。因此，本综述讨论了 tau 靶向免疫疗法研究的更新、AD 相关的 tau 物种、有希望的生物标志物的更新以及以有效和及时的方式围绕疾病传播的联合疗法的前景。